Post-menopausal women who use estrogens generally experience at once a reduced risk of coronary heart disease and, at the same time, and increased risk of endometrial cancer. In order to protect the endometrium from unopposed estrogens, most authors now recommend the addition of a progestin during 10-13 days of the cycle. Progestins are probably responsible for the increased risk of myocardial infarction (MI) in women on oral contraceptives. Does the addition of progestins pose a risk for fatal and non-fatal MI in post-menopausal women on estrogens? To assess the risk from progestins, we have designed a population-based, case-control study. The setting is Group Health Cooperative (GHC). We will use the computerized files at GHC to identify potential cases: all post- menopausal women, aged 40 to 79 yrs, will be eligible as cases if, according to the WHO criteria, they present with a fatal or non- fatal MI. A random sample of women listed in the enrollment files at GHC will serve as our source of potential controls. Review of the out-patient medical records, performed by an assistant blind to case-control status, will ensure that all study subjects meet the same entrance criteria. This effort will also secure information about potential confounding factors. Using a pictorial display of estrogens and progestins mailed to those who give informed consent, we will also rely on telephone interviews to obtain information about exposure to post-menopausal hormones as well as known risk factors. The computerized pharmacy records at GHC will provide additional information about exposure. Frequency matching will control for the potential confounding effects of age and year of presentation, and data analysis will involve the techniques of stratification and logistic regression. Collecting data for 6 years--2 retrospectively and 4 prospectively--will identify a number of study participants sufficient to provide 80% power for detecting a relative risk of 1.75. The use of population-based controls, moreover, will enhance the validity of our findings--results which will form part of an argument about the overall risk or benefit from the use of progestins, as well as estrogens, in post-menopausal women.